4-163350313-G-C

Variant names:

• chr4-163350313-G-C
• rs745630054
• NM_006174.4:c.40G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006174.4(NPY5R):​c.40G>C​(p.Ala14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,442,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: NPY5R NM_006174.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.674
• Publications: 1 publications found

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07777074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006174.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	NM_006174.4	MANE Select	c.40G>C	p.Ala14Pro	missense	Exon 4 of 4	NP_006165.1	Q15761
	NPY5R	NM_001317091.2		c.40G>C	p.Ala14Pro	missense	Exon 4 of 4	NP_001304020.1	Q15761
	NPY5R	NM_001317092.2		c.40G>C	p.Ala14Pro	missense	Exon 5 of 5	NP_001304021.1	Q15761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	ENST00000338566.8	TSL:1 MANE Select	c.40G>C	p.Ala14Pro	missense	Exon 4 of 4	ENSP00000339377.3	Q15761
	NPY5R	ENST00000506953.1	TSL:6	c.40G>C	p.Ala14Pro	missense	Exon 1 of 1	ENSP00000423474.1	Q15761
	NPY5R	ENST00000515560.1	TSL:2	c.40G>C	p.Ala14Pro	missense	Exon 4 of 4	ENSP00000423917.1	Q15761

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244252 AF XY: 0.0000227

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1442986 Hom.: 0 Cov.: 31 AF XY: 0.00000839 AC XY: 6 AN XY: 715310

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.00 AC: 0 AN: 42666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25454

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39304

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099694

Other (OTH) AF: 0.0000168 AC: 1 AN: 59402

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.9
DANN	Benign	0.88
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.67
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.21
Sift	Benign	0.27	T
Sift4G	Benign	0.19	T
Polyphen		0.10	B
Vest4		0.13
MutPred		0.36		Gain of disorder (P = 0.0562)
MVP		0.68
MPC		0.26
ClinPred		0.038	T
GERP RS		2.6
PromoterAI		-0.0091	Neutral
Varity_R		0.058
gMVP		0.53
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745630054; hg19: chr4-164271465;